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Electrophysiological, Morphological, and Topological Properties of Two Histochemically Distinct Subpopulations of Cerebellar Unipolar Brush Cells

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Abstract

Unipolar brush cells (UBCs) are excitatory cerebellar granular layer interneurons whose brush-like dendrites receive one-to-one mossy fiber inputs. Subclasses of UBCs differ primarily by expressing metabotropic glutamate receptor (mGluR) 1α or calretinin. We used GENSAT Tg(Grp-EGFP) BAC transgenic mice, which selectively express enhanced green fluorescent protein (EGFP) in mGluR1α-positive UBCs to compare the functional properties of the two subclasses. Compared to EGFP-negative UBCs, which include the calretinin-positive cells, EGFP-positive UBCs had smaller somata (area 48 vs 63 μm2), lower specific membrane resistance (6.4 vs. 13.7 KΩ cm2), were less prone to intrinsic firing, and showed more irregular firing (in cell-attached ~49 % were firing vs. ~88 %, and the CV was 0.53 vs. 0.32 for EGFP-negative cells). Some of these differences are attributable to higher density of background K+ currents in EGFP-positive cells (at −120 mV, the barium-sensitive current was 94 vs. 37 pA in EGFP-negative cells); Ih, on the contrary, was more abundantly expressed in EGFP-negative cells (at −140 mV, it was −122 vs. −54 pA in EGFP-positive neurons); furthermore, while group II mGluR modulation of the background potassium current in EGFP-negative UBCs was maintained after intracellular dialysis, mGluR modulation in EGFP-positive UBCs was lost in whole-cell recordings. Finally, cell-attached firing was reversibly abolished by the GABAB activation in EGFP-positive, but not in EGFP-negative UBCs. Immunohistochemistry showed that EGFP-negative UBCs express GIRK2 at high density, while mGluR1α UBCs are GIRK2 negative, suggesting that GIRK2 mediates the mGluR-sensitive current in EGFP-negative UBCs. These data suggest that the two subclasses perform different functions in the cerebellar microcircuits.

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Acknowledgments

This work was supported by NIH grant RO1 09904. Paraffin embedding and sectioning of the paraffin-embedded blocks was performed by Northwestern University Mouse Histology and Phenotyping Laboratory, which is supported by a Cancer Center Support Grant (NCI CA060553). The authors wish to thank Drs. Joe P. Doyle, Joseph D. Dougherthy, and Nataniel Heintz, The Rockefeller University, New York, NY, for breeding pairs of Tg(Grp-EGFP)DV197 mice.

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No conflict of interest exists for any of the authors.

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Authors and Affiliations

  1. Department of Physiology, Northwestern University, Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL, 60611, USA

    Jin-Ah Kim, Enrico Mugnaini & Marco Martina

  2. Department of Cell and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA

    Gabriella Sekerková & Enrico Mugnaini

  3. Knowles Hearing Center, School of Communication, Northwestern University, 2240 Campus Drive North, Evanston, IL, 60208, USA

    Gabriella Sekerková & Enrico Mugnaini

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  1. Jin-Ah Kim
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  2. Gabriella Sekerková
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Correspondence to Marco Martina.

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Kim, JA., Sekerková, G., Mugnaini, E. et al. Electrophysiological, Morphological, and Topological Properties of Two Histochemically Distinct Subpopulations of Cerebellar Unipolar Brush Cells. Cerebellum 11, 1012–1025 (2012). https://doi.org/10.1007/s12311-012-0380-8

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  • DOI: https://doi.org/10.1007/s12311-012-0380-8

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